The following Structured Product Label (SPL) was submitted to the FDA by Amneal Pharmaceuticals Llc for the product Calcium Chloride (NDC 70121-2308). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2.1 important administration instructions, 2.2 recommended dosage and administration, 2.3 recommended starting dose in patients with renal impairment, 2.4 drug incompatibilities, 3 dosage forms and strengths, 4 contraindications, 5.1 end-organ damage due to intravascular ceftriaxone-calcium precipitates, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
Calcium chloride injection is indicated for the treatment of adult and pediatric patients with acute symptomatic hypocalcemia.
Limitations of Use
The safety and effectiveness of calcium chloride injection for long-term use has not been established.
Administer calcium chloride injection by slow intravenous infusion in a central or deep vein in adults and pediatric patients (with or without renal impairment); do not administer by bolus [see Warnings and Precautions (5.2, 5.4)]. The maximum recommended infusion rate is 1 mL/minute (100 mg/minute).
Additional important administration instructions regarding calcium chloride injection are as follows:
The recommended dose range of calcium chloride injection in:
Dosing of this calcium chloride injection product is not possible in patients who require doses less than 200 mg because the recommended dose cannot be achieved with the supplied syringe. For patients who require doses less than 200 mg, use another calcium chloride injection product that allows dosing of less than 200 mg.
Individualize the dose for a patient within these dose ranges depending on serum ionized calcium level, severity of hypocalcemia symptoms and the acuity of hypocalcemia onset.
Repeated injections may be required because of rapid excretion of calcium.
The recommended starting dose of calcium chloride injection in [see Use in Specific Populations (8.6)]:
Do not mix calcium chloride injection with other drugs simultaneously. Do not mix calcium chloride injection with ceftriaxone or administer these products simultaneously via a Y-site because concurrent use can lead to the formation of ceftriaxone-calcium precipitates [see Warnings and Precautions (5.1)]:
Calcium Chloride Injection, USP (single-dose) supplied as:
The 100 mg/mL concentration represents 27 mg or 1.4 mEq of elemental calcium per mL of solution.
Calcium chloride injection is contraindicated in:
Newborns (up to 28 days of age) if they require (or are expected to require) ceftriaxone intravenous treatment because of the risk of precipitation of ceftriaxone-calcium, regardless of whether these products would be received at different times or through separate intravenous lines [see Warnings and Precautions (5.1)].
The use of calcium chloride injection is contraindicated in newborns (up to 28 days of age) if they require (or are expected to require) ceftriaxone intravenous treatment because of the risk of precipitation of ceftriaxone-calcium, regardless of whether these products would be received at different times or through separate intravenous lines [see Contraindications (4)]. Cases of fatal reactions with calcium-ceftriaxone precipitates in lungs and kidneys in premature and full-term newborns aged less than 1 month have occurred when ceftriaxone and calcium were administered either simultaneously or non-simultaneously and through different intravenous lines. In-vitro studies demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium compared to other age groups.
In patients older than 28 days of age, calcium chloride injection and ceftriaxone intravenous solutions may be administered sequentially one after another if infusion lines at different sites are used, infusion lines are replaced, or infusion lines are thoroughly flushed between infusions with physiological salt solution to avoid precipitation. Do not mix or administer calcium chloride injection simultaneously with ceftriaxone, even if using different infusion lines or different infusion sites as it can lead to precipitation of ceftriaxone-calcium [see Dosage and Administration (2.4)].
Rapid injection of calcium chloride injection may cause vasodilation, decreased blood pressure, bradycardia, arrhythmias, syncope and cardiac arrest. It is particularly important to prevent a high concentration of calcium from reaching the heart because of the risk of syncope. Too rapid an injection exceeding 1 mL/minute may lead to hypotension and cardiac syncope [see Dosage and Administration (2.1)].
Arrhythmias may occur if calcium chloride injection and digoxin are administered together. Hypercalcemia resulting from an overdose of calcium chloride injection increases the risk of digoxin toxicity. Avoid the use of calcium chloride injection in patients receiving digoxin. If concomitant therapy is necessary, closely monitor ECG and calcium levels [see Drug Interactions (7.1)].
Administration of calcium chloride injection in patients with local trauma may result in calcinosis cutis due to transient increase in local calcium concentration. Calcinosis cutis can occur with or without extravasation of calcium chloride injection, is characterized by abnormal dermal deposits of calcium salts and clinically manifests as papules, plaques, or nodules that may be associated with erythema, swelling, or induration. Tissue necrosis, ulceration and secondary infection are the most serious complications.
To minimize the risk of tissue necrosis, ulceration and calcinosis, administer calcium chloride injection slowly through a small needle into a large vein [see Dosage and Administration (2.1)]. Avoid extravasation or accidental injection into perivascular tissues. Should perivascular infiltration occur, immediately discontinue intravenous administration at that site and treat as needed.
Calcium chloride injection contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature (preterm) neonates and preterm infants, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day can accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower amounts of aluminum.
Exposure to aluminum from calcium chloride injection at the recommended dose is not more than 10 mcg [see Dosage and Administration (2.2) and Description (11)]. When prescribing calcium chloride injection in patients receiving parenteral nutrition solutions, limit the total daily patient exposure to aluminum to no more than 5 mcg/kg/day.
The following serious adverse reactions are also described elsewhere in the labeling:
The following adverse reactions have been identified in literature and post-marketing reports of calcium chloride. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
Avoid the concomitant use of calcium chloride injection with digoxin. If concomitant use is unavoidable, monitor ECG closely during administration of calcium chloride injection.
Synergistic arrhythmias may occur with concomitant use. The use of calcium chloride injection may result in hypercalcemia which increases the risk of digoxin toxicity [see Warnings and Precautions (5.3)].
Concomitant use of calcium chloride injection and calcium channel blockers may reduce the response to calcium channel blockers. Avoid concomitant use. If concomitant use is unavoidable, monitor blood pressure closely during administration of calcium chloride injection.
Increase frequency of monitoring of calcium concentrations in patients taking concomitant calcium chloride injection and other drugs that increase the risk of hypercalcemia (e.g., calcipotriene, estrogen, lithium, parathyroid hormone, teriparatide, thiazide diuretics, Vitamin A and Vitamin D).
Risk Summary
Administration of calcium chloride injection for the treatment of acute symptomatic hypocalcemia during pregnancy is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with development of hypocalcemia during pregnancy (see Clinical Considerations). Animal reproduction studies have not been conducted with calcium chloride injection.
The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-associated Maternal and/or Embryo/Fetal/Neonatal Risk
Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor and possibly preeclampsia. Infants born to mothers with hypocalcemia can develop fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures.
Risk Summary
Calcium is present in human milk. Administration of the approved recommended dose of calcium chloride injection to the mother is not expected to cause harm to a breastfed infant. There is no information on the effects of calcium chloride injection on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for calcium chloride injection and any potential adverse effects on the breastfed infant from calcium chloride injection or from the underlying maternal condition.
The safety and effectiveness of calcium chloride injection for the treatment of acute symptomatic hypocalcemia have been established in pediatric patients.
The use of calcium chloride injection is contraindicated in newborns if they require (or are expected to require) ceftriaxone intravenous treatment because of the risk of precipitation of ceftriaxone-calcium, regardless of whether these products would be received at different times or through separate intravenous lines [see Contraindications (4) and Warnings and Precautions (5.1)].
In pediatric patients older than 28 days of age, calcium chloride injection and ceftriaxone intravenous solutions may be administered sequentially one after another if infusion lines at different sites are used, infusion lines are replaced, or infusion lines are thoroughly flushed between infusions with physiological salt solution to avoid precipitation. Do not mix or administer calcium chloride injection simultaneously with ceftriaxone, even if using different infusion lines or different infusion sites as it can lead to precipitation of ceftriaxone-calcium.
Calcium chloride injection contains aluminum that may be associated with central nervous system and bone toxicity. Because of immature renal function, preterm infants receiving prolonged parenteral nutrition treatment with calcium chloride injection may be at higher risk of aluminum toxicity [see Warnings and Precautions (5.2)].
Clinical studies of calcium chloride injection did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
The use of calcium chloride injection in patients with renal impairment may increase the risk of a higher calcium-phosphorus product. For patients with renal impairment, initiate calcium chloride injection at the lowest recommended dose within the recommended dose range [see Dosage and Administration (2.2)]. Monitor serum calcium levels frequently based on the severity of the renal impairment and the risk of a high calcium-phosphorus product (e.g., every 4 hours).
Overdosage of calcium chloride injection may lead to hypercalcemia. Symptoms of hypercalcemia typically develop when the total serum calcium concentration is ≥ 12 mg/dL and include shortening of QT interval, bradycardia, hypertension, anorexia, nausea, vomiting, bowel hypomotility and constipation, muscle weakness, bone pain, decreased concentration, depression, weakness, fatigue, confusion, hallucinations, disorientation, hypotonicity, seizures and coma. Hypercalcemia effects on kidney include diminished ability to concentrate urine and diuresis.
In the event of overdosage, promptly discontinue calcium chloride injection, the patient should be re-evaluated and appropriate countermeasures should be instituted, if necessary [see Warnings and Precautions (5), Adverse Reactions (6)].
10% Calcium Chloride Injection, USP is a sterile, nonpyrogenic, hypertonic, clear, colorless solution for single administration only. Each mL contains 100 mg (1.4 mEq/mL) of calcium chloride, dihydrate (1.4 mEq each of Ca++ and Cl−) in water for injection. It is provided in a 10 mL single-dose syringe and 10 mL single-dose vial for intravenous injection. The solution contains no bacteriostat, antimicrobial agent or added buffer. The pH of 10% calcium chloride injection, USP is between 5.5 to 7.5 when diluted with water for injection to make a 5% solution. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. The osmolar concentration is 2.04 mOsmol/mL (calc.). 10% calcium chloride injection, USP is oxygen sensitive.
Calcium chloride dihydrate, USP is chemically designated CaCl2 • 2H2O (dihydrate) and its structural formula is as below:
1 (Calcium Chloride Injection Usp 1000 mg Per 10 mL 1)
It appears as white, hard, odorless fragments or granules. It is deliquescent. It is very soluble in boiling water, freely soluble in water, in alcohol and in boiling alcohol.
Calcium chloride injection, USP contains no more than 1,000 mcg/L of aluminum [see Warnings and Precautions (5.2)].
Intravenous administration of calcium chloride increases serum ionized calcium concentration. Calcium chloride dissociates into ionized calcium in plasma.
The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of calcium chloride injection have not been fully characterized.
Absorption
Calcium chloride injection is 100% bioavailable following intravenous injection.
Distribution
Calcium in the body is distributed mainly in skeleton (99%) and 1% is distributed within the extracellular fluids and soft tissues. About 50% of total serum calcium is in the ionized form and represents the biologically active part; 8% to 10% serum calcium is bound to organic and inorganic acid, respectively; and approximately 40% is protein-bound (primarily to albumin).
Elimination
Metabolism
Calcium itself does not undergo direct metabolism.
Excretion
Calcium is excreted by the kidney through a combination of glomerular filtration and tubular reabsorption. A significant increase in urinary excretion of calcium was observed during and after intravenous infusion of calcium chloride.
Specific Populations
The effect of age, sex, race, ethnicity, renal or hepatic impairment on the pharmacokinetics of calcium have not been evaluated in clinical studies.
Carcinogenicity, mutagenicity and fertility have not been assessed with calcium chloride injection.
10% Calcium Chloride Injection, USP is a clear, colorless solution supplied as follows:
| Unit of Sale and Product Description | Strength | NDC |
|---|---|---|
10 mL Single-Dose Glass Syringe in 1 Carton Unit of 24 | 1,000 mg/10 mL (100 mg/mL) | NDC 70121-2308-1 NDC 70121-2308-4 |
10 mL Single-Dose Vial 10 x 10 mL Single-Dose Vials in 1 Carton | 1,000 mg/10 mL (100 mg/mL) | NDC 70121-2309-1 NDC 70121-2309-7 |
The 100 mg/mL concentration represents 27 mg or 1.4 mEq of elemental calcium per mL of solution.
Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Inform patients or caregivers of the following risks of calcium chloride injection:
Arrhythmias with Concomitant Digoxin Use
Arrhythmias may occur if calcium chloride injection and Digoxin are administered together [see Warnings and Precautions (5.3)].
Tissue Necrosis and Calcinosis
Administration of calcium chloride injection may result in calcinosis cutis including tissue necrosis, ulceration and secondary infection. [see Warnings and Precautions (5.4)].
Aluminum Toxicity
Calcium chloride injection contains aluminum that may be toxic [see Warnings and Precautions (5.5)].
10 mL Single-Dose Pre-Filled Syringe is Manufactured by:
Amneal Pharmaceuticals Pvt. Ltd.
Ahmedabad 382213, INDIA
10 mL Single-Dose Vial is Manufactured by:
Amneal Pharmaceuticals Pvt. Ltd.
Ahmedabad 382110, INDIA
Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807
Rev. 07-2024-01
NDC 70121-2308-1
10% Calcium Chloride Injection USP, 1,000 mg/ 10 mL (100 mg/mL)
10 mL Syringe Label
Rx only
Amneal Pharmaceuticals LLC
2 (Calcium Chloride Injection Usp 1000 mg Per 10 mL 2)
NDC 70121-2308-1
10% Calcium Chloride Injection USP, 1,000 mg/ 10 mL (100 mg/mL)
10 mL Syringe Carton Label
Rx only
Amneal Pharmaceuticals LLC
3 (Calcium Chloride Injection Usp 1000 mg Per 10 mL 3)
NDC 70121-2308-4
10% Calcium Chloride Injection USP, 1,000 mg/ 10 mL (100 mg/mL)
24 x 10 mL Syringe Carton Label
Rx only
Amneal Pharmaceuticals LLC
4 (Calcium Chloride Injection Usp 1000 mg Per 10 mL 4)
NDC 70121-2309-1
10% Calcium Chloride Injection USP, 1,000 mg/ 10 mL (100 mg/mL)
10 mL Vial Label
Rx only
Amneal Pharmaceuticals LLC
3 (Calcium Chloride Injection Usp 1000 mg Per 10 mL 5) 
NDC 70121-2309-7
10% Calcium Chloride Injection USP, 1,000 mg/ 10 mL (100 mg/mL)
10 x 10 mL Vial Carton Label
Rx only
Amneal Pharmaceuticals LLC
4 (Calcium Chloride Injection Usp 1000 mg Per 10 mL 6) 
* Please review the disclaimer below.
